1. Field of the Invention
This invention relates to a pharmaceutical composition for preventing and treating allergic diseases and to a method for preparation thereof. Specifically, the present invention relates to a pharmaceutical composition comprising Platycodi Radix, Scutellariae Radix, Ponciri Fructus, Schizonepetae Herba, Bupleuri Radix, Angelicae dahuricae Radix, Paeoniae Radix alba, Cnidii Rhizoma, Angelicae gigantis Radix, Ledebouriellae Radix, Forsythiae Fructus, Glycyrrhizae Radix, Lonicerae Flos, Taraxaci Herba, Trichosanthis Radix, Ulmi Cortex Radicis, Astragali Radix, Atractylodis Rhizoma alba, Rehmanniae Rhizoma, Zanthoxyli Fructus, Magnoliae Flos, Xanthii Fructus, Mori Cortex Radicis, Pinelliae Tuber, Cimicifugae Rhizoma, Puerariae Radix and Menthae Herba as the active ingredients for preventing and/or treating acute and/or chronic allergic nasal diseases (including chronic paranasal sinusitis), allergic dermatitis, allergic otitis media (including recurrent otitis media with effusions), allergic conjunctivitis, allergic asthma, etc., and to a method for preparation thereof.
2. Description of the Prior Art
A normal immune reaction may cause local inflammations or eliminate foreign substance without damaging tissues of their hosts by stimulating effective molecules to remove attacks from allergen through various mechanisms. However, the term of hypersensitivity or allergy is used when an immune reaction is excessively activated or progressed in an undesirable direction to harm the human body. Today, allergic diseases cost a lot of money, because they tend to be more severe in civilized societies. According to a literature [Scientific American, September, 1993], more than 20% of American people are suffering from various allergic symptoms, and allergic rhinitis is the most common form of allergy. The attack of allergen can sometimes be fatal. According to the statistical data of 1990, it was reported that 3.6 billion dollars had been spent to the direct medical cost for asthma. As to the number of patients who are suffering from these allergic diseases, Korea is also on the similar level to the developed countries. The number is increasing every year. In particular, young child patients are on rapid increase. Thus, many researchers are devoting themselves in developing a drastic cure to reduce economic, biological and physical burden of the patient from such allergic diseases.
It might be said that diversity and complexity of allergic diseases are from the exposure to many kinds of allergen in the modern life. Synthetic fibers such as nylon and Teflon, and synthetic resins such as polyethylene, polyester and epoxy resin, which brought innovation to the textile industry, cause anaphylactic contact dermatitis at skin or mucous membrane by various chemical substances like monomer and polymer that are produced in the manufacturing process. On the other hand, allergic inflammations on the skin are caused by contact with glass frames, artificial teeth, wrist watch chains, plastic raincoats, umbrella handles, etc. The substances such as polyurethane, which are widely used as paints for cars, furniture and musical instruments, are the main cause of bronchial asthma. Rubber, leather, cement, and metals such as platinum, gold, mercury and nickel may cause allergic contact dermatitis. Accessories, such as earrings, necklace and finger rings, or rubber products, may also cause allergy. It is well known that fast food, antiseptic, synthetic sweetening, and additives including food colors may also cause food allergy.
Moving into the age of synthetic medicine from that of natural medicine in which raw materials were the roots of herbs and the barks of trees, antibiotic shocks and drug allergies by chemical substances (e.g. sulfas, salicylic acids, pyrazolon and local anesthetic) and enzymatic substances have been frequently occurred. It has been revealed that the pathogenesis of food and drug allergy could occur in all types of hypersensitivity immune reactions I, II, III, and IV. Allergy to cosmetic materials has become common. Bronchial asthma has been rapidly increased since the environmental pollution has caused or worsened respiratory allergic diseases. Today, occupational allergies also draw our attention. We can take numerous examples of such occupational allergies as bakery asthma, dandruff asthma, librarian asthma of librarians, wood asthma of carpenters, poultry farming asthma, and contact dermatitis of welders.
The initial stage of allergic reaction is development of IgE antibody that makes a strong combination with the mast cell or receptors on the surface of basophilic leukocyte. After the antigen (allergen) eaten by antigen-presenting cells such as macrophages was processed, the peptide presented by MHC class II molecule on the surface of membrane is recognized by receptors on the surface of T-cell(TCR). Cell-activating substance (cytokines), such as IL-2, IFN-v and TNF (tumor necrosis factor)-xcex2(derived from Th1-cells), and IL-4, IL-5, IL-6, IL-9 and IL-10 (derived from Th2-cells), are produced in the activated T-cells. The produced cell-activating substance acts on T and B cells to participate in proliferation and differentiation. Then, B-cells are activated by the combination of CD40 ligand (CD40L) on T-cells and CD 40 on B-cells. Furthermore, as IL-4 derived from T-cells is added, B-cells are differentiated into IgE-producing cells by a class switch. In the mast cells, two molecules of IgE are combined with polyvalent antigen to form a bridge on the receptors of membrane, leading to a series of biochemical processes causing degranulation. Various chemical media such as histamine are secreted from the mast cell by degranulation, and may increase the permeability of capillary, contract the smooth muscle, and enhance the mucus secretions, together with prostaglandins and leukotrienes produced newly by arachidonic acid metabolism within the membrane, which results in the followings: pruritis, flare, urticaria and angioedema on the skin; coughing, suffocating, chest tightness, respiratory difficulties. and cyanosis in the respiratory tract; paling, hypotension and arrhythmia in, cardiovascular system; nausea, vomiting and diarrhea in GI tract; and paresthesia, vertigo, headache, convulsion and loss of consciousness in the nerve system.
Chronic paranasal sinusitis as an example of allergic disease, which frequently occurs in an allergic constitution, may cause a nasal polyp when nasal hypertrophy gets more severe by irreversible changes such as desquamation, regression and coagulation of the blood vessel to the epidermis of mucous membrane on occurring the repetitive acute paranasal sinusitis. The chronic paranasal sinusitis poorly responds to internal medicines including antibiotic, and surgical operations for young children are not recommended because the paranasal sinuses of young children are in the development. Although adult patients can get surgical operations for the chronic paranasal sinusitis, the disease may easily recur if a drastic treatment for cold is not accompanied by immune reinforcement.
Also, otitis media is another common disease that occurs more than once in 70% of the infants, and about 10% of acute otitis media are progressed to the chronic stage in spite of antibiotic treatment. The recurrent otitis media with effusions (ROMEs) occurs when young children with weak immunity are exposed to upper respiratory infection before chronic otitis media are completely cured. The ROMEs tend to be increased if prolonged and may cause severe posteffects such as hearing disturbance, adhesion of tympanic membrane, and destruction of bone structure. In the young children with allergic constitution and weak immunity, the repeated colds by virus and secondary bacterial infection serve as complicated factors for ROME together with chronic paranasal sinusitis, adenoid hypertrophy, and middle ear ventilation problem by eustachian obstruction.
The medicines used currently in alleviating various allergic symptoms have the problem that the effects thereof are temporary, and some side effects may occur by a long-term therapy. The antibiotics cannot affect the inhibition of IL-6 that is known for playing an important role in pathogenesis of chronic mucous exudates that are progressed in young children. A report shows that IL-6 could be controlled through antibiotic and steroids for a long period of time. However, administration of antibiotics and steroids for a long time may cause such side effects as suppressing immune function of the whole body.
The present inventors have made extensive clinical researches and experiments in view of a medical treatment method of Bujungkusa (curing pathogenic factors by encouraging normal immune power of the human body) with the intention to prevent and cure various allergic diseases in a radical way without any side effect. As a result, the inventors have found that a suitable combination of specific herbs has an excellent antiallergic effect without common side effects above mentioned, and completed the present invention. In particular, the composition according to the present invention may increase immunity to cure paranasal sinusitis, control allergy, and minimize the possibility for young children to catch colds.
The present invention provides a pharmaceutical composition for preventing and treating allergic diseases comprising an extract of mixture including Platycodi Radix, Scutellariae Radix, Ponciri Fructus, Schizonepetae Herba, Bupleuri Radix, Angelicae dahuricae Radix, Paeoniae Radix alba, Cnidii Rhizoma, Angelicae gigantis Radix, Ledebouriellae Radix, Forsythiae Fructus, Glycyrrhizae Radix, Lonicerae Flos, Taraxaci Herba, Trichosanthis Radix, Ulmi Cortex Radicis, Astragali Radix, Atractylodis Rhizoma alba, Rehmanniae Rhizoma, Zanthoxyli Fructus, Magnoliae Flos, Xanthii Fructus, Mori Cortex Radicis, Pinelliae Tuber, Cimicifugae Rhizoma, Puerariae Radix and Menthae Herba. Preferably, the present composition further comprises more than one selected from a group consisting of Atractylodis Rhizoma, Aurantii Nobilis Pericarpium, Amomi Semen, Myristicae Semen, Mume Fructus, Asiasari Radix, Akebiae Caulis, Raphani Semen and Cocicis Semen.
The active ingredients of the present composition have the following effects and/or fuction: Platycodi Radix has expectorant and/or drain, and defervescence effects; Scutellariae Radix has anti-inflammatory, defervescence, analgesic, antiseptic, antihypersensitivity, and antiviral effects; Ponciri Fructus has effects of relieving stagnation and antiallergic effect; Schizonepetae Herba has anti-inflammatory effects for, pharyngitis, and itching relieving, and antimicrobial effects; Bupleuri Radix has sweat-promoting and digesting, spasmolytic, analgesic, defervescence, mucolytic, and anti-inflammatory effects; Angelicae dahuricae Radix has nasal obstruction relieving, detumescence and analgesic effects; Paeoniae Radix alba has sedative, spasmolytic, defervescence, analgesic, antimicrobial, anti-inflammatory and vasodilatory effects; Cnidii Rhizoma has effects of promoting healing and blood flow; Angelicae gigantis Radix has blood-nourishing and moistening, sedative, analgesic and antimicrobial effects; Ledebouriellae Radix has calming, analgesic, antimicrobial and anti-inflammatory effects; Forsythiae Fructus has calming, anti-inflammatory, drain, analgesic, vitalizing and detumescence effects; Glycyrrhizae Radix has mucolytic, expectorant, detoxification, spasmolytic, anti-inflammatory, analgesic and antihypersensitivity effects; Lonicerae Flos has calming, detoxification, vitalizing and blood flow promoting effects; Taraxaci Herba has calming, detoxification, anti-inflammatory, antimicrobial, antiviral, antifungal, and diuresis effects; Trichosanthis Radix has fluid producing, moistening, detumescence, and drain effects; Ulmi Cortex Radicis has detumescence, detoxification, antipyretic, and anti-inflammatory effects; Astragali Radix. has Ki-replenishing, toxin weakening, drain and, analgesic effects; Atractylodis Rhizoma alba has spleen-tonificating and replenishing, drying and diuresis, and sweat-suppressing effects; Rehmanniae Rhizoma has calming, blood-tonificating and fluid producing effects; Zanthoxyli Fructus has effects for warming the spleen and stomach to dispel cold and relieving nasal obstruction; Magnoliae Flos and Xanthii Fructus have effects for removing cold sense and relieving nasal obstruction; Mori Cortex Radicis has effects for purging heat the lung and anti-asthma, diuresis and detumescence; Pinelliae Tuber has effects for moistening and expectorant; Cimicifugae Rhizoma has effects for calming and detoxification; Puerariae Radix has an effect of vitalizing, and Menthae Herba has wind-dispelling, antipyretic, and throat-refreshing effects.
The additional ingredients of the present composition have the following effects: Atractylodis Rhizoma has effects for invigorating spleen and drying; Aurantii Nobilis Pericarpium has vitalizing and drying, expectorant, antitussives, and mucolytic effects; Amomi Semen has drying and healing-promoting, spleen-warming and diarrhea-relieving effects; Myristicae Semen has spleen-warming, healing-promoting, astringent and diarrhea-relieving effects; Mume Fructus has anti-inflammatory, astringent and fluid-producing effects; Asiasari Radix has effects for warming lung and resolving phlegm, diverging wind-cold and analgesic; Akebiae Caulis has effects for promoting normal flow and emaciation; Raphani Semen has effects for promoting digestion, checking upward perverted Ki, and expectorant; Cocicis Semen has calming, drain, emaciation, detumescence, invigorating spleen, and anti-inflammatory effects.
The present composition contains Platycodi Radix, Scutellariae Radix, Ponciri Fructus, Schizonepetae Herba, Bupleuri Radix, Angelicae dahuricae Radix, Paeoniae Radix alba, Cnidii Rhizoma, Angelicae gigantis Radix, Ledebouriellae Radix, Forsythiae Fructus, Glycyrrhizae Radix, Lonicerae Flos, Taraxaci Herba, Trichosanthis Radix, Ulmi Cortex Radicis, Astragali Radix, Atractylodis Rhizoma alba, Rehmanniae Rhizoma, Zanthoxyli Fructus, Magnoliae Flos, Xanthii Fructus, Mori Cortex Radicis, Pinelliae Tuber, Cimicifugae Rhizoma, Puerariae Radix and Menthae Herba, preferably in a ratio of 4-6:2-4:3:3:3:3:4-6:4:4-8:2:2-6:4-8:6-12:8-12:4:6-12:6-10:4-8:4-8:2:2-4:4-6:4-6:4:2-4:4-8:2. The present composition further contains more than one selected from the group consisting of Atractylodis Rhizoma, Aurantii Nobilis Pericarpium, Amomi Semen, Myristicae Semen, Mume Fructus, Asiasari Radix, Akebiae Caulis, Raphani Semen and Cocicis Semen preferably in a ratio of 4:4:4:4:2-4:2:3:4:8-10.
The present inventors through many clinical and animal experiments have determined the ratio of the ingredient herbs. In the event that the proportion of each herb is below the lower limit of proportion, its pharmaceutical effect is drastically decreased. On the other hand, if it is above the higher limit of proportion, synergistic and cooperative effects among ingredient herbs are decreased due to decrease of pharmacological effects of other ingredients.
The pharmaceutical composition of this invention may be used for preventing and treating allergic diseases such as acute or chronic allergic rhinitis (including chronic paranasal sinusitis), allergic dermatitis, allergic otitis media (including ROME), allergic conjunctivitis, and allergic asthma. These pharmacological effects of the present composition are proved by Experiments 1-4 below. The pharmacological mechanism of the present composition has not been exactly revealed yet, but can be inferred that the present composition suppresses local and systemic allergic reactions of the human body by controlling generation of cell-activating substances and chemical media produced in the immune cells.
The pharmaceutical composition of the present invention may be prepared by mixing pharmaceutically acceptable carriers with the extract of mixture including Platycodi Radix, Scutellariae Radix, Ponciri Fructus, Schizonepetae Herba, Bupleuri Radix, Angelicae dahuricae Radix, Paeoniae Radix alba, Cnidii Rhizoma, Angelicae gigantis Radix, Ledebouriellae Radix, Forsythiae Fructus, Glycyrrhizae Radix, Lonicerae Flos, Taraxaci Herba, Trichosanthis Radix, Ulmi Cortex Radicis, Astragali Radix, Atractylodis Rhizoma alba, Rehmnanniae Rhizoma, Zanthoxyli Fructus, Magnoliae Flos, Xanthii Fructus, Mori Cortex Radicis, Pinelliae Tuber, Cimicifugae Rhizoma, Puerariae Radix and Menthae Herba. The extract may be obtained by decocting herbal medicines with conventional suitable solvents according to physical and chemical properties, and may be concentrated and dried to powder.
The present composition may be formulated into the forms of pills, granules, spray, liquid, etc., using conventional preparation methods. The present composition is preferably in a form of liquid in view of effectiveness, but it may be prepared in the form of pills, granules, spray, suppository, tablet, or capsules, and may be changed to any other form, if desired.
The present composition may be prepared by the following method: for example, adding 1000 ml of water to the mixture including 4-6 g of Platycodi Radix, 2-4 g of Scutellariae Radix, 3 g of Ponciri Fructus, 3 g of Schizonepetae Herba, 3 g of Bupleuri Radix, 3 g of Angelicae dahuricae Radix, 4-6 g of Paeoniae Radix alba, 4 g of Cnidii Rhizoma, 4-8 g of Angelicae gigantis Radix, 2 g of Ledebouriellae Radix, 2-6 g of Forsythiae Fructus, 4-8 g of Glycyrrhizae Radix, 6-12 g of Lonicerae Flos, 8-12 g of Taraxaci Herba, 4 g of Trichosanthis Radix, 6-12 g of Ulmi Cortex Radicis, 6-10 g of Astragali Radix, 4-8 g of Atractylodis Rhizoma alba, 4-8 g of Rehmanniae Rhizoma, 2 g of Zanthoxyli Fructus, 2-4 g of Magnoliae Flos, 4-6 g of Xanthii Fructus, 4-6 g of Mori Cortex Radicis, 4 g of Pinelliae Tuber, 2-4 g of Cimicifugae Rhizoma, 4-8 g of Puerariae Radix and 2 g of Menthae Herba, optionally with 4 g of Atractylodis Rhizoma, 4 g of Aurantii Nobilis Pericarpium, 4 g of Amomi Semen, 4 g of Myristicae.Semen, 2-4 g of Mume Fructus, 2 g of Asiasari Radix, 3 g of Akebiae Caulis, 4 g of Raphani Semen and 8 -10 g of Cocicis Semen, and decocting the mixture for 1.5 hour to be concentrated to 150 ml of decoction. The suitable dose is 1.5-2 ml per kg of body weight and is administrated 3 times a day. For example, a young child weighted 20 kg takes 30-40 ml of the decoction 3 times a day. However, the dose of the present composition is varied depending on weight, age, sex, seriousness of disease, and a patient""s ability to digest. Further, the other formulation of the present composition may be administrated orally or parenterally by an appropriate dose.
In taking the present composition, patients with chronic allergic disease should take it consecutively for an average of 3 months, ones with a chronic paranasal sinusitis for an average of 4 months, ones with allergic ROME for an average of 3 months, and ones with atopic dermatitis for an average of 5 months.
The present invention will be explained in detail by the following Examples, which are not intended to limit the present invention.